Adenosine receptor agonists: Synthesis and binding affinity of 2-(aryl)alkylthioadenosine derivatives

Abstract

The synthesis of a new series of 2-(aryl)alkylthio derivatives of N-ethylcarboxamido adenosine (NECA) is described, in comparison with the corresponding derivatives of adenosine. Binding studies (A1, A 2A, and A3) and adenylyl cyclase activity (A 2B) at human adenosine receptor) subtypes stably transfected in Chinese hamster ovary (CHO) cells showed that the 2-(aryl)alkylthioadenosine derivatives are more potent than the corresponding NECA derivatives at A 1 receptors, while the NECA derivatives possess highest affinity at both A2A and A3 receptors. Thus, the 2-(1-pentyl)thioadenosine (7) with a Ki A1 = 91 nM, the 2-phenylethylthioNECA (18) with a KiA2A = 24 nM, and the 2-phenylmethylthioadenosine (11) with a KiA3 = 68 nM, could be useful tools to be modificated in order to find very potent and selective agonists for the human adenosine receptor subtypes.